Cartridge for electrohemodialysis

ABSTRACT

The scope of the invention is to apply an electric current or to use a kind of iontophoresis system with the hemodialysis cartridge and system (the proposed method is also applicable to peritoneal dialysis or other similar methods) to remove unwanted molecules from blood, plasma or serum or other body fluids and to increase the effectiveness of the process. This cartridge can be used for patients with uremia and cartridge fixed to the conventional hemodialysis machine and additionally the electric current applied to the electrodes placed in to the cartridge or electrode connectors placed to the conventional cartridge. When the system activated, the molecules in the blood or other body fluid migrates to the hemodialysis solution. Charged ions or uncharged molecules move together with electroosmotic flow. The sterilized electrodes preferably made by Ag/AgCl to prevent pH changing effect. Other apparatus can also be used for providing an electropotential gradient.

BACKGROUND OF THE INVENTION

This invention is related to a cartridge and/or a method that provides an additional step of iontophoresis to conventional/classic hemodialysis procedure for those patients who have insufficient kidney functions. It enhances the hemodialysis performance in removing of urea from the blood using electrical potentials. Similarly, it is also related with the procedures such as peritoneal dialysis or related with the procedure when some compounds or molecules (charged or uncharged atoms or molecules, elements or ions) need to be removed from the blood (blood, plasma or serum) to dialysis solution in acute or chronic poisoning cases. It is possible to increase the efficiency of the hemodialysis method and to reduce the total time period of the procedure using this proposed cartridge and/or the method. There are no similar procedures and/or cartridges in use so far.

DESCRIPTION OF THE INVENTION

Basically, hemodialysis is a process to remove urea and some other toxic compounds from blood into the hemodialysis solution by passive diffusion. In this procedure, a semi-permeable membrane is used as a dialysis membrane. While the blood is circulating continuously at the one side of the hemodialysis membrane, the hemodialysis solution at the other side, continuously circulates as well. During the process, urea present in the blood at high concentration, depending on the concentration gradient, it passes through the membrane from blood to the hemodialysis solution. Thus, the urea concentration in blood decreases by the time. In conventional hemodialysis procedures, the patient is connected to the hemodialysis machine for about 4 hours, and urea concentration generally decreases to 50% of the beginning level even at the best circumstances.

In iontophoresis procedure, by using an electrical current (creating an electrical potential difference), the ions (molecules or atoms that having a net charge or partially charged) can be carried to the other side of the membrane according to applied current and electrical charge and it is possible to control it. Electrodes or similar tools are provided to the both side of the membrane and the applied electrical current or potential can vary as needed. The ions in the solution/blood migrate according to their charges and their movement is in proportional to the current. For instance positively charged ions migrate to the negative electrode side and vice versa. While the charged ions are migrating according to the electrical current, they also drag the uncharged molecules along with moving molecules. At this instance, traveling from one side to the other side of the membrane creates a flow, a turbulence occurs (this is called an electro-osmotic flow).¹ Therefore the unchanged particles (atoms/molecules) can also be able to pass through the membrane by being pulled into this vortex or into the motion and, this passage occurs at a much faster rate than that of passive diffusion.

When the molecular structure of urea investigated, it is seen that some local charges are present on the molecule. According to the experiments we've conducted, the higher urea transportation was observed than passive diffusion and cathodal iontophoresis when urea was present at the positive electrode side because of the positive local charges on the molecule. There is also a possibility that the electroosmotic current was partially influential for this transfer. However, during the transfer, if the other small but charged ions like potassium and sodium are present, the transfer rate decreases; but still the transfer is much larger and faster than the classical method. These experiments were repeated using human blood obtained from the patients with uremia and similar results were achieved. With this invention the hemodialysis procedure is shortened in time and, simultaneously, provided much better result (cleaner blood).

The previously conducted diffusion experiments were repeated with a peristaltic pump using human blood, hemodialysis solution and the hemodialysis cartridge in new proposed design. In the analysis of the samples taken from the blood that went through the cartridge, it is found that the urea level in blood when the iontophoresis procedure was used prompted 3 to 5 times faster rate of decrease than the classical hemodialysis results. In other words, while the classical hemodialysis procedure takes 4 hours, the iontophoresis procedure of ours lowers the process time to about 30 minutes, and with much better results (FIG. , 1).

If the classical hemodialysis cartridge and proposed iontophoresis procedure is going to be used together; system is depicted in FIG. 2. The cartridge used as a hemodialysis cartridge for removing urea from the blood simply comprises a holding compartment (FIG. -2-1- and FIG. -3-1); and because of the electrodes placed in the cartridge, (FIG. -2-A and B; FIG. -3-A and B) electric current can be applied and that, it is also designed for the use of classical hemodialysis cartridge.

Accordingly, in this figure, the point labeled as 1 indicates the entry of blood and the label 2 shows the exit of the blood. The labels 3 and 4 show the entry and exit points of the hemodialysis solution. The label 5 shows the hemodialysis cartridge's dialysis membrane. The label B shows positive electrode, and label A represents the negative electrode. Thus, when the system is activated, the blood and hemodialysis solution is circulating continuously and electric current is applied and at the end urea can be transferred to the hemodialysis solution with much faster rate. The labels A and B are the electrodes made by Ag and AgCl or they can be designed for same purpose in different shape or compositions. If needed, it is possible to use Ag for B, and AgCl for A. UV or ethylene oxide sterilization can be used for the sterilization of the electrodes.

On the other hand, although the composition of the sterilized electrodes (FIG. -2-A and B; FIG. -3-A and B) is preferred to be Ag/AgCl for preventing the pH effect of the electrodes, they can be also made out of platinum, copper, gold, steel, graphite, vanadium, tungsten, etc. The composition, shape, design, connection point and their place in and outside of the cartridge, are not deterministic and specific properties for the electrodes. Some apparatuses which can be used in formation of electrical gradient may be utilized.

In the experiments, when the electrohemodialysis procedure was used, the sodium and potassium levels of the blood and the hemodialysis solutions have been analyzed. When this procedure used, the level of sodium and potassium is lowered in blood as well. This outcome is possibly same for some other ions and unchanged molecules. For preventing some possible complications, the ions and other material in the hemodialysis solution need to be adjusted. Hemodialysis solutions must be prepared according to the patients' needs. Or, the blood that exited from the hemodialysis cartridge can be connected to another cartridge and similarly ions can be replaced using reverse current and the problem can be solved. The hemodialysis solution(s) (at the beginning and at the supplementary durations) can be prepared according to the needed requirements of the patient to avoid any possible complications.

Additionally, in these complications (the problems like imbalance of electrolytes and/or osmotic pressure or similar unwanted outcomes due to iontophoresis) problems can be overcame by producing a membrane that would have smaller pores. With two membranes present in one, first one allows the unwanted urea and the other molecules does not allowed by second material to go through. The application of electrical current to both membrane or by applying the classical methods to the second one (utilizing only the concentration gradient) the possible problems can be avoided.

There is no research and experiments that have been published so far, the application of electrical current or potential and the gradual electrical effect have not been tried for the hemodialysis or peritoneal dialysis or removing unwanted molecules, ions etc. from the blood or other body fluid using a system like our proposed system here. In this study, the addition of iontophoresis procedure, in terms of shortening the time duration and bettering the quality of outcome, is a revolutionary format that is at the cutting edge of the known medical technology. In the literature there is no study or research have been conducted to this end.

This invention, in addition to its speed and quality in the treatment of uremia, it has a high potential of removing unwanted/unneeded non-polar and especially polar substances during the acute and chronic poisoning; similarly with electrical current and the cartridge usage the unwanted items/substances in the blood can be pulled out into the hemodialysis solution. In the literature we came across that the electrical current lesser than 0.5 mA/cm² does not cause damage to the blood or body cells¹. For this reason the current that is low than 0.5 mA/cm² would be an acceptable for a positive out come. The magnitude of the current can be chosen in required levels. For the system, direct or alternative current, square, sinus or triangular or even different frequencies and/or currencies can be applied. In this system, the electrical flow/current does not make any direct contact with any of the body cells; and therefore, it would be possible to exceed the electrical level of the aforementioned literature. However, because there is a likelihood of damaging the blood cells during a high currency flow this would not be recommended.

Additionally, the pH levels was not affected by the Ag/AgCl electrodes, therefore we preferred. Electrodes can be made with different compounds or also some similar apparatuses with similar functions can be used. The electrodes may even be simply attached to the classical hemodialysis cartridges' blood and hem-dialysis solution's entry ports (FIG. 3). If the available classical hemodialysis cartridge will be used, an alternative placement of the electrodes are shown in FIG. 3. In this model, the electrodes can be attached to blood entry port and hemodialysis solution part as in the previous cases, and the classical hemodialysis cartridge can be used with minimal modifications. (In this model, electrodes in different composition or some apparatus with similar functions can be used). The electrodes themselves need to be sterilized. In FIG. 3, the labels 1,2,3,4 and 5 are the same labels as shown in FIG. 2.

As a result, this invention will prevent those patients who have insufficient kidney functions being hooked up to a hemodialysis machine for a long time. It will provide for the urea, creatine, and some toxic compounds to exit the blood in a better way. Additionally, the procedure's potential of removing the unwanted elements from the patient's blood stream in acute and chronic poisonings will provides a very valuable device in the field of medicine.

With the exception of electrodes and similar apparatuses, the cartridge being proposed, in terms of shape and dimensions is very similar to those cartridges used in classical hemodialysis. The difference of the cartridge, such as surface area or its membrane with different pore sizes, alone is not a distinctive quantification of the proposed device for patent purposes. The sizes, compositions, or locations (such as one being by the blood inflow side and the other being by the dialysis side or the solution) of the electrodes and/or some apparatuses with similar functions do not restrict its applicability for patent rights.

Additionally, the composition of the hemodialysis solution, the properties of the dialysis membrane (color, texture, latex or biological tissue, pore size, selectivity, etc.), the way, the flow intensity and the direction of the blood, hemodialysis solution and the number of cartridge used connected before or after each other are not also deterministic and specific properties of the invention.

Reference

-   1—M. J. Pikal, “The role of electro-osmotic flow in transdermal     iontophoresis,” Advanced Drug Delivery Reviews, 46, 281-305,2001. 

1. A method for transferring undesired substances from a blood/plasma to a solution prepared with a predetermined content by circulating the blood/plasma at one site of a separating membrane and the solution at the other site of the separating membrane, comprising the steps of: a) applying constant electrical current with a certain charge to the site where blood/plasma is circulated and applying an opposite-charged constant electrical current to the other site where said solution is circulated so that undesired charged substances in the blood/plasma are transferred through said membrane into the solution by electrical forces and accordingly the neutral or partially charged substances are also transferred to the solution by means of an electroosmotic flow obtained by the movement of the charged substances, whereby higher flow rate is achieved compared to the passive diffusion; b) optionally, for replacing some substances, which were previously transferred in the step (a) from the blood/plasma to the solution, back to the blood/plasma, preparing solutions not directly in contact with the system defined in the step (a) and applying a reverse electrical current compared to the step (a) to the solutions and blood/plasma; and c) maintaining the step (a) and optionally step (b) until the desired amount of removal of undesired substances from blood/plasma is achieved.
 2. A method according to claim 1, wherein, in the step (a), a positive constant electrical current is applied to the site blood/plasma circulating site and similarly a negative constant electrical to the solution site.
 3. A method according to claim 1, wherein the steps (a) and optionally step (b) are achieved by the process of ionotophoresis.
 4. A method according to claim 1, wherein the step (b) can “also” be performed only by the passive diffusion.
 5. A method according to any one of the preceding claims, where electrical currents such as pulsative square waves, sinus waves or triangular waves or waves in different frequencies and wave types or any direction of the current or any separating membrane can also be applied and used.
 6. A method according to any of the preceding claims, wherein the level of said electrical current ideally is not exceeding 0.5 mA/cm².
 7. A method according to any of the preceding claims, wherein the electrical current applied is not directly in contact with the tissues.
 8. A method according to any of the preceding claims, wherein it is used for the treatment of renal failure cases, acute and chronic poisoning cases, and peritoneal dialysis.
 9. A method according to claim 1, wherein said undesired substances in blood are urea, keratin, and poisoning or other toxic substances.
 10. A method according to claim 1, wherein said partially charged substance in blood is urea.
 11. A method according to claim 1, wherein said substances to be replaced with (or) in the blood/plasma are sodium, potassium, certain uncharged substances and certain ions.
 12. A method according to any one of the preceding claims, wherein the electrical current is applied to the blood/plasma and the solution through at least two electrodes: one positioned the blood/plasma circulating site, and the other positioned in the solution site.
 13. A method according to claim 1, wherein, to perform the step (a), at least one electrohemodialysis cartridge or a ‘device’ to house the said process of the claim 1 is used, said cartridge or device comprising at least one membrane selected according to the undesired substance(s), at least one blood/plasma compartment where the blood/plasma is circulated and at least one solution compartment where the solution prepared according to the undesired substances is circulated, said blood/plasma compartment being separated from the solution compartment by said membrane, at least one electrode positioned in the blood/plasma compartment or optionally in the inlet part thereof and at least one oppositely charged electrode fixed in the solution compartment or optionally in the inlet part thereof.
 14. A method according to claim 1, wherein, to perform the step (b), at least one another electrohemodialysis cartridge or a device to house the aforementioned process of the claim 1 is used; said cartridge or device comprising at least one membrane selected according to the substances to be replaced to the blood/plasma, at least one blood/plasma compartment where the treated blood/plasma is circulated; at least one solution compartment where the solution prepared according to the substances to be replaced, is circulated; and, said blood/plasma compartment being separated from the solution compartment by said membrane.
 15. A method according to claim 14, where said another electrohemodialysis Cartridge or device also comprises at least one electrode which is positioned in said blood/plasma compartment or optionally in the inlet parts thereof and at least one electrode which is placed in the solution compartment or optionally in the inlet parts thereof, said electrodes being oppositely charged compared to the electrodes of the claim
 13. 16. A method according to any one of claims 12 to 15, wherein Ag and AgCl electrodes are used in order to prevent any undesired changes in pH.
 17. A method according to any one claims 12 to 16, wherein, any conventionally available electrohemodialysis cartridges or devices can be used.
 18. A method according to any one of the preceding claims, characterized in that it works under ambient temperature.
 19. A method according to any one of the preceding claims, wherein the working solution to collect undesired molecules/substance is conventionally available hemodialysis solution and composition thereof is predetermined according to the needs by dilution or the working solution is a buffered or unbuffered solution in terms of pH and it's composition is adjusted according to the needs.
 20. An electrohemodialysis cartridge or device, for enabling molecule or substance transfer between blood/plasma and a hemodialysis solution with a content prepared according to the patient's needs, having a membrane a blood compartment the blood/plasma is circulated therein, a hemodialysis solution compartment the hemodialysis solution is circulated therein, said blood/plasma compartment being separated from said hemodialysis solution compartment, characterized by comprising an electrode positioned in the blood/plasma compartment or optionally in the inlet part thereof and an oppositely charged electrode positioned in the hemodialysis solution compartment or optionally in the inlet part of the cartridge.
 21. An electrohemodialysis cartridge or device according to claim 20, characterized in that said electrodes being made of a material selected from the group of materials comprising Ag, AgCl, platinum, copper, gold, steel, graphite, vanadium, tungsten
 22. An electrohemodialysis cartridge or device according to claim 20, characterized in that the electrode positioned in said blood/plasma compartment is an Ag electrode and that positioned in the hemodialysis solution compartment is an AgCl electrode.
 23. An electrohemodialysis cartridge or device according to claim 20, characterized in that some apparatuses which can be used in formation of electrical current may be utilized instead of said electrodes.
 24. An electrohemodialysis cartridge or device according to claims 20 and 23, characterized in that the electrodes or said apparatus can be placed at the inlet part or outlet part of the cartridge or one being in the blood inflow side, the other at the dialysis solution inflow side.
 25. An electrohemodialysis cartridge or device according to claim 20, characterized in that it further comprises a further membrane with smaller pores for preventing some necessary ions and uncharged molecules apart from the urea from flowing to the hemodialysis solution.
 26. An electrohemodialysis cartridge or device according to claim 20, characterized in that positively charged electrode (B) is placed in the solution compartment and negatively charged electrode (A) is placed in blood/plasma compartment for removing the other charged or uncharged atoms or molecules from the blood.
 27. An electrohemodialysis cartridge or device according to claim 20, characterized in that the applied electrical current is lower than 0.5 mA/cm².
 28. An electrohemodialysis cartridge or device according to claim 20, characterized in that it comprises a secondary cartridge, the blood exited from the primary cartridge is connected thereto, with the same structure of the primary cartridge for replenishing sodium, potassium and some necessary ions back to the blood/plasma exited from the primary cartridge by applying reverse electrical current thereto, said secondary cartridge also having hemodialysis solution(s) prepared according to ions and substances to be replenished. 